The aim of this investigation was to hypothesize that 17β-estradiol(estrogen)can modulate the production and activity of reactive oxygen species(ROS), nitric pxide(NO)synthasis, and lipid peroxidation in fibroblast-like synovial cells, and the effects are dependent on the expressions of estrogen receptor alpha(ER-α).The results showed that the combined treatment of cytokines and estrogen for the high ER-α expressed fibroblasts decreased the intracellular ROS and NO generation, lipid peroxidation production and subsequent prevented apoptotic cell death, although the low expressed ER-α cells did not show the substantial change.The experiments on levels of iNOS mRNA confirmed the NO levels.These results suggest that estrogen plays an important role in protecting cells against cytokine-induced cell death by controlling the generation of NO and ROS and lipid peroxidation.